This proposed project has a twofold purpose: (1) to study the conformational changes that occur in membrane protein and lipid as a consequence of the interaction of a neurotransmitter (dopamine) with its receptor (striatal synaptic plasma membrane); and (2) to study the mechanism for "blockade" of this neurotransmitter:receptor interaction by neuroleptic compounds. The techniques involved employ electron spin resonance spectroscopy and spin labels specific for particular areas of membrane lipid and protein to monitor the dopamine:receptor interaction. In addition, methods which utilize uniqe spin labeled analogs of chlorpromazine (CPZ) and dopamine are proposed to determine the membrane location of CPZ and the physical environment of the dopamine receptor binding site, respectively.